1. Field of the Invention
The field of the present invention is bone repair and replacement. The invention relates to cohesive, formable, and injectable demineralized bone powder compositions, in particular, for use in implantation.
2. Description of the Relevant Art
Bone grafts are used to correct osseous defects that may be caused by trauma, pathological disease, surgical intervention or other situations. It is preferred to have the defect filler in the form of a stable, moldable putty to facilitate the placement of the bone growth medium into an osseous site, which is usually uneven in shape and depth. The medical specialist will take the putty on a spatula or other instrument and trowel it into the site or take it in his/her fingers and shape the bone inducing material into the proper configuration to fit or pack into the site being corrected.
The use of demineralized bone matrix (DBM) powder in the repair of bone defects has been a subject of investigation for some time. DBM is an osteogenic and osteoinductive material most commonly obtained from long bone chips demineralized by acid treatment. The acid treatment dissolves inorganic mineral components and acid-soluble proteins in the bone, leaving behind a collagen matrix as well as acid-insoluble proteins and growth factors. Among the remaining acid-insoluble proteins and growth factors are bone morphogenic proteins (BMPS) and transforming growth factors (TGFs). DBM is a desirable component of bone graft materials because it provides an osteoinductive matrix and exhibits osteoconductive potential, thereby promoting bone growth and healing (e.g. WO 00/45870). Moreover, DBM is fully resorbable, and bone graft materials containing organic DBM are highly biocompatible because it contains many of the components of natural bone. Advantageously, DBM costs less than many other available organic bone composition additives, such as isolated BMPs.
DBM is usually available in a lyophilized or freeze dried and sterile form to provide for extended shelf life. The bone in this form is usually very coarse and dry and is, therefore, not conducive to surgical manipulation.
U.S. Pat. No. 5,073,373 discloses a deformable, shape-sustaining osteogenic composition, in which DBM particles are dispersed within a liquid polyhydroxy carrier, such as glycerol. The vast majority of the DBM particles possess random, irregular geometries with an average median length to median thickness ratio of from about 1:1 to about 3:1. The combination of the glycerol's high water solubility and reduced viscosity causes the composition to be “runny” and to flow away from the site almost immediately after placement, thus preventing the proper retention of the composition at the implant site (U.S. Pat. No. 6,030,635).
Bone particles having a median length to median thickness ratio of at least about 10:1 have been used in osteogenic compositions (U.S. Pat. Nos. 5,314,476, 5,510,396 and 5,507,813). These elongated particles have a median length of from about 2 mm to at least about 400 mm and a median thickness from about 0.05 mm to about 2 mm. The DBM fibers are commercially available as a preformed fiber sheet, matrix, or workable putty from Osteotech Corporation (Shrewsbury, N.J.) under the trade names Grafton® DBM Putty, Grafton® DBM Flex, and Grafton® DBM Matrix. Although the use of long DBM fibers improves both the bulk viscosity and the handling characteristics of a glycerol mixture, U.S. Pat. No. 5,510,396 indicates the mixture still lacks cohesiveness. The mixture's rapid dissipation rate due to the miscibility of the glycerol carrier in aqueous environments remains a problem. The larger DBM particles may also retard the development of new bone by the patient because the large particles do not pack as well as the smaller, grainy particles of bone. This leaves more open space in the mixture and lengthens the time required to grow new bone and properly fill the defect.
In order to address the lack of cohesiveness of DBM at implant sites, the use of binders, such as carboxymethyl cellulose, or the use of high molecular weight hydrogels or other polymers as carrier vehicles has been reported (U.S. Pat. Nos. 6,030,635 and 6,340,477). However, these binders can negatively affect the biocompatibility and osteoinductivity of the DBM composition. Furthermore, these binders provide cohesiveness to the composition only prior to its implantation; following implantation, these binders are eroded or dissolved from the implant site and, consequently, the implant does not retain its shape in vivo.
The ability of a DBM composition to retain its shape during and after implantation is desirable so that it is able to resist erosion when used as an implant, for example, at an osseous or semi-osseous defect site.